Niflumic acid Property

Melting point:

203-204 °C

Boiling point:

378.0±42.0 °C(Predicted)

Density 

1.3935 (estimate)

storage temp. 

2-8°C

solubility 

Soluble in ethanol (~50 mg/ml), acetone (50 mg/ml, Clear to Slightly Hazy, Yellow), methanol (~50 mg/ml), DMSO (56 mg/ml at 25°C), and acetonitrile (~50 mg/ml).

pka

pKa 2.26 ± 0.08;4.44± 0.03(H2O,t =25±0.1,I=0.01(NaCl))(Approximate)

form 

Solid

color 

Light orange to Yellow to Green

Water Solubility 

19mg/L(room temperature)

Sensitive 

Light Sensitive

Merck 

14,6531

Stability:

Stable, but may discolour in light. Incompatible with strong oxidizing agents. Hygroscopic.

InChIKey

JZFPYUNJRRFVQU-UHFFFAOYSA-N

NIST Chemistry Reference

Niflumic acid(4394-00-7)

EPA Substance Registry System

3-Pyridinecarboxylic acid, 2-[[3-(trifluoromethyl)phenyl]amino]- (4394-00-7)

Safety

Hazard Codes 

Xn

Risk Statements 

20/21/22-36/37/38

Safety Statements 

26-36-36/37/39

RIDADR 

UN 2811 6.1/PG 3

WGK Germany 

3

RTECS 

QT2999100

HazardClass 

6.1

PackingGroup 

Ⅲ

HS Code 

29333999

Toxicity

LD50 in rats (mg/kg): 370 orally; 155 i.p. (Sorenson)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H301Toxic if swalloed

H413May cause long lasting harmful effects to aquatic life

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P273Avoid release to the environment.

P301+P310IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.

P405Store locked up.

P501Dispose of contents/container to..…

Niflumic acid Chemical Properties,Usage,Production

Chemical Properties

Crystalline Solid

Originator

Nifluril,U.P.S.A.,France,1968

Uses

analgesic, antiinflammatory

Uses

Niflumic acid is used for the exact same indications as the drugs described above. Synonyms for this drug are actol, flunir, nifluril, and others.

Uses

Anti-inflammatory. Selective cyclooxygenase-2 (COX-2) inhibitor

Definition

ChEBI: Niflumic acid is an aromatic carboxylic acid and a member of pyridines.

Manufacturing Process

Niflumic acid is prepared as follows: Nicotinic acid, m-trifluoromethylaniline, and potassium iodide are intimately mixed and heated on an oil bath at 140°C. The mixture melts to give a dark red liquid. The temperature of the oil bath is allowed to fall to 100°C and is maintained at this temperature for an hour and a half. The mixture puffs up and forms a yellow crystalline mass. After cooling to ordinary temperature, this mass is ground up in a mortar and extracted several times with small volumes of ether to remove excess mtrifluoromethylaniline. The residue is then washed twice with 10 ml of distilled water to remove m-trifluoromethylaniline hydrochloride and potassium iodide, and finally twice with 10 ml of 95% alcohol to remove colored resinous contaminants. After drying at 100°C, 2-(m-trifluoromethylanilino)nicotinic acid is obtained as pale yellow needles (from 70% ethanol) melting at 204°C (Kofler block).

Therapeutic Function

Antiinflammatory

Trade name

Actol (Mayrhofer, Austria; Upsamedica, Spain), Donalgin (Gedeon Richter, Hungary), Livornex (Genepharm, Greece), Ni- flam (Upsamedica, Italy), Nifluril (UPSA, France; Upsamedica, Belgium, Switzerland, Portugal).

Biochem/physiol Actions

Niflumic acid (NFA), a γ-aminobutyric acid type A receptor (GABAARs) antagonist is a non-steroidal anti-inflammatory drug (NSAID) and it belongs to the fenamate class. It is also a blocker of chloride ion channel and a calcium-activated chloride channel (CaCC) inhibitor. NFA possesses anti-inflammatory property and is useful in treating rheumatic disorders. It is also an inhibitor of N-methyl-D-aspartate receptor and glycine receptor. NFA also inhibits enzymes associated with the prostaglandins synthesis.

Side effects

Niflumic acid has been used effectively to treat rheumatoid arthritis, psoriatic arthritis, and hypertrophic osteoarthritis of the hip and knee. Gastric complications are the chief adverse effects of this drug.

Synthesis

Niflumic acid, 2-3-(trifluoromethyl)anilino nicotinic acid (3.2.21), is synthesized either by the reaction of 2-chloronicotinic acid with 3-trifluoromethylaniline [84¨C86], or 2-aminonicotinic acid with 1-bromo-3-trifluoromethylbenzene [87].